Can we predict the metastatic potential of papillary microcarcinoma by immunohistochemical evaluation of CD73, CD147 and osteopontin?

Aim: Papillary thyroid microcarcinomas, which generally has favourable disease outcome, can metastasise to lymph nodes occasionally. Lymph node metastasis is one of the best indicators for disease recurrance. Increased expression of CD73, CD147 and Osteopontin (OPN) antibodies have been shown to be related with the adverse prognostic factors in malignant tumors, such as lymph node metastasis, advanced tumor stage and decreased survival. Our purpose is to define the association between the immunhistochemical expression of CD73, CD147 and OPN antibodies and presence of lymph node and/or distant metastasis in papillary thyroid microcarcinomas. Further we examine the relevance of lymph node metastasis with age, sex, tumor diameter, tumor border features, lymphatic, vascular and perineural invasion. Materials and methods: Two hundered forty eight papillary thyroid microcarcinoma cases, which were older than 18 years old, had unicentric and larger than 5 mm tumors and diagnosed between 2006-2019 at Istanbul University, Istanbul Faculty of Medicine, Department of Pathology, were selected. The proper fields of each tumor were signed on the slides and new paraffin blocks were created from the original blocks through using tissue microarray (TMA) process. Immunohistochemistry assays for CD73, CD147 and OPN anitbodies performed on new slides, which were prepared from TMA blocks. Further we evaluated and scored immunohistochemical expressions according to the extensity and intensity of expressions and defined H-score which was calculated by multiplying the extensity and intensity scores. Prognosis data for each case was achieved from General Surgery, Endocrinology and Nuclear Medicine departments, thereby the cases with or without lymph node and/or distant metastasis were defined. Additionally, histomorphological parameters of the cases were noted from the pathology reports. Results: There were 20 (8,1%) lymph node metastasis and 2 (0,08%) distant metastasis (mediastinal lymph node) among 248 cases. Eighteen of cases, which had lymph node metastasis, were classical type, 1 case was Warthin-like variant and 1 case was diffuse sclerosing variant. Two cases with distant metastasis were classical type. Lymph node metastasis were significantly more frequent in classical type, males, older than 50 years, tumors that is larger than 7 mm, tumors with lymphatic invasion and infiltrative borders. Capsule invasion or perineural invasion were not relevant with lymph node metastasis. Tumors that fulfilled the criteria of NIFT-P, hadn't got any lymph node metastasis. In immunohistochemistry evaluation, CD73 showed apical and rarely membraneous expression. The expression in ≥80% of tumor cells or intensity score 3 or H-score ≥190, were found relevant with lymph node metastasis. Some of the cases with intensity score 3 revealed membraneous staining pattern, which was not mentioned before, for thyroid tumors. Furthermore, lymph node metastasis is significantly more frequent in cases with membraneous staining. CD147 showed cytoplasmic and membraneous staining. Intensity and/or extensity score of CD147 expression was not correlated with metastasis. OPN showed cytoplasmic staining. The expression in ≥50% of tumor cells or intensity score 2 and 3 or H-score ≥100 were found relevant with lymph node metastasis. Conclusion: Lymph node metastasis was significantly more frequent in patients older than 50 years, males, tumors that are larger than 7 mm or tumors that have lymphatic invasion and infiltrative borders. When the expression of CD73 and OPN immunohistochemistry were extensive and severe, lymph node metastasis was observed significantly more frequently. Besides, membraneous expression of CD73 was significantly relevant with lymph node metastasis. Expression of CD147 was not correlated with metastasis. It has showed that CD147 expression hasn't got any significance with lymph node metastasis.